Our overall objective is to interrelate the time course during and after cessation of a systolic and diastolic overload to the myocardium with the compensatory hemodynamic, electrophysiological, biochemical, sympathetic nervous system and ultrastructural alterations in newborn and adult animals and humans. Thermodilution, nuclear, and contrast angiographic techniqes will be used to study ventricular function resulting from balloon obstruction of the pulmonary artery and/or aorta in the conscious dog. The following will be studied: 1) the neural and pharmacological pathways of the autonomic nervous system in the production of pulmonary hypertension by balloon distention of the pulmonary artery, 2) the physiopharmacology and metabolic fate of norepinephrine in the pathogenesis of ventricular hypertrophy particularly in the model for Hypertrophic "Obstructive" Cardiomyopathy, 3) using the long term infusion technique, various humoral substances important in the hypertrophy process will be studied and chemical substances which may be efficacious in the therapy of heart failure will be tested. A major goal has been to discover the structural basis for acute and chronic overload to the heart differentiating "physiological" from "pathological" hypertrophy; emphasis replaced on 1) the intercalated disc - (multiple, widened, and separated intercalated discs), 2) fractionation of actin filaments, 3) ribosomes, 4) mitochondria and 5) sarcoplasmic reticulum. Myocardial biopsy will be obtained from patients and dogs with systolic and diastolic ventricular overloads to relate structure with function. Determinants of the growth characteristics of the myocardium in tissue culture will be studied.